A short and flexible route to aza-beta-(1 -> 6)-C-disaccharides: Selectivealpha-glycosidase inhibitors

The syntheses of azaMan-beta-(1-->6)-C-Glc (4), azaGlc-beta-(1-->6)-C-Glc ( 5), and azaGal-beta-(1-->6)-C-Glc (6) based upon double reductive amination of acetylenic carbohydrate-derived diketones is described. The required di ketones are obtained by addition of the acetylenic sugar anion derived from dibromoolefin 7 to benzyl-protected mannopyranolactone, glucopyranolactone , or galactopyranolactone, followed by reduction of the ketose and oxidatio n of the resulting diol. Ensuing double reductive amination and hydrogenoly sis affords the target compounds in reasonable to good yields. Enzyme inhib ition tests show that neither of the three compounds 4, 5, and 6 inhibit be ta-glycosidases, while moderate to good inhibitory activities were found on alpha-glycosidases, the most active being 6 (alpha-galactosidase: K-i = 0. 092 mu M).